Dystonia is a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements, or abnormal postures. Dystonia can be classified by etiology into primary (or idiopathic) and secondary (or symptomatic). The etiology in most cases of dystonia is idiopathic. Idiopathic dystonic may be inherited or sporadic in occurrence. Family members of patients with inherited, idiopathic, generalized dystonia may have generalized, segmental or focal dystonia and generalized dystonia typically begins focally suggesting that the idiopathic dystonias may have a common pathophysiology. Postmortem pathologic examination and magnetic resonance imaging have been unrevealing in patients with idiopathic dystonia. Neurochemical study of postmortem brains from a few patients with idiopathic dystonia has demonstrated abnormalities in serotonin and norepinephrine levels in various brain regions. However, it is not clear whether or not these abnormalities are merely epiphenomenal. The dystonic (dt) rat is an autosomal recessive mutant with a motor syndrome that closely resembles the generalized dystonia seen in humans. The dystonic rat undergoes a period of normal development prior to the emergence of a motor syndrome characterized by twisting of the axial musculature and limbs. The nervous system is normal on examination with light microscopy and the abnormal movements are reduced or absent with rest. The features of the dystonic rat suggest that it may be a useful model of idiopathic, generalized dystonia and possibly idiopathic dystonia in general. In the dystonic rat marked biochemical and physiological abnormalities have been isolated to the olivo-cerebellar pathways. The specific aims of the research proposal are to further characterize the abnormalities in the dt rat olivo-cerebellar pathways and to determine the importance of cerebellar outflow in the generation of the dt rat motor syndrome. The three neuron loop from the inferior olive to the Purkinje cells of cerebellar cortex to the deep cerebellar nuclei will be examined systematically, beginning with the inferior olive. Biochemical and physiological findings in this species may provide insight into human dystonia.